Spectroscopic MRI-Guided Radiation Therapy Planning in Glioblastoma

NCT03137888 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: IRB00094188NCI-2017-00424RAD3383-17R01CA214557P30CA138292
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This pilot clinical trial studies the side effects of spectroscopic magnetic resonance imaging (MRI)-guided radiation therapy and how well it works in treating patients with newly-diagnosed glioblastoma or gliosarcoma. Spectroscopic MRI can show doctors where the extent of tumor is in the brain beyond current clinical MRI scans by mapping areas of high tumor metabolism. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Spectroscopic MRI-guided radiation therapy may work better in treating patients with glioblastoma or gliosarcoma.

Conditions

Glioblastoma; Gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Feasibility as Assessed by Successful Co-registration of sMRI-based Treatment Volumes With Clinical Images Into the Radiation Treatment Execution Platform

  Feasibility of this approach will be determined by whether treatment volumes based on sMRI can be co-registered with clinical images and transferred into the radiation treatment execution platform in a seamless manner, so that sMRI information can be efficiently applied to the patient treatment.

  Up to 2 years after completion of therapy

• Incidence of Adverse Event Assessed by Common Terminology Criteria for Adverse Events Version 4.0

  The safety of sMRI to guide dose-escalated RT will be confirmed by assessing toxicity potentially attributable to the RT.

  Up to 2 years after completion of therapy

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  2 years from the start of RT.

Other Outcomes (1)

• Overall Survival (OS)

  2.5 years from start of RT

Study Arms (1)

sMRI-Guided RT with TMZ

EXPERIMENTAL

Patients undergo spectroscopic magnetic resonance imaging-guided dose-escalated radiation therapy daily for the first 5 days of every week (Monday - Friday) over 6 weeks. Patients also receive standard of care temozolomide PO daily during radiation therapy for up to 42 days.

Radiation: Dose-Escalated Radiation Therapy; Procedure: Spectroscopic Magnetic Resonance Imaging; Drug: Temozolomide

Interventions

Dose-Escalated Radiation Therapy RADIATION

Undergo sMRI-guided radiation therapy, dose painted to maximum of 75 Gy over six weeks

Also known as: RT, Radiation Therapy

sMRI-Guided RT with TMZ

Spectroscopic Magnetic Resonance Imaging PROCEDURE

Patients will undergo sMRI scans within a 14 day window prior to starting treatment

Also known as: sMRI, MRSI, Magnetic Resonance Spectroscopic Imaging

sMRI-Guided RT with TMZ

Temozolomide DRUG

Given PO

Also known as: Methazolastone, Temcad, Temodal, Temodar, Temomedac, TMZ

sMRI-Guided RT with TMZ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically by a board-certified neuropathologist
• Patients must be able to have MRI scans
• Patients must have the following lab values ≤ 14 days prior to registration:
• White blood cell (WBC) ≥ 3,000/µL
• Absolute neutrophil count (ANC) ≥ 1,500/µL
• Platelet count of ≥ 75,000/µL
• Hemoglobin ≥ 9.0 gm/dL (transfusion is allowed to reach minimum level)
• Serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2.0 x upper limit of normal (ULN)
• Bilirubin ≤ 2 x ULN
• Creatinine ≤ 1.5 mg/dL
• Patients must have a life expectancy of ≥ 12 weeks
• Patients must have a Karnofsky performance status (KPS) ≥ 60
• Patients who are women of childbearing potential must have a negative pregnancy test documented ≤ 14 days prior to registration; this is not specific to dose escalation and is mandatory for standard care for patients being treated with radiation therapy; the cost of this test will be covered by standard of care
• Patients must be able to understand and provide written informed consent
• Members of all races and ethnic groups are eligible for this trial; subjects will be approximately representative of the demographics of the referral base for the participating institutions

You may not qualify if:

• Patients with pacemakers, aneurysm clips, neurostimulators, cochlear implants, metal in ocular structures, history of being a steel worker, or other incompatible implants which makes MRI safety an issue are excluded
• Patients that have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are excluded
• Patients with a history of any other invasive cancer (except non-melanoma skin cancer and excluding carcinoma in-situ), unless in complete remission and off of all therapy for that disease for ≥ 3 years, are ineligible
• Patients with an active infection or serious intercurrent medical illness are ineligible
• Patients receiving any other investigational agents are excluded
• Patients who have received prior cytotoxic, non-cytotoxic or experimental drug therapies for brain tumor are excluded
• Patients with a history of prior cranial radiation are ineligible
• Patients may not be enrolled on any other therapeutic trial for which they are receiving an anti-tumor therapy
• Patients with GBMs located in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: mesial temporal lobe, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum
• The maximum radiation target volume for gross tumor volume 3 (GTV3) is 65 cc (per NRG Oncology guide); patient may be excluded after the first sMRI scan if the GTV3 volume is greater than 65 cc (we anticipate that contrast-enhancing tumor volume \[residual tumor volume following tumor resection\] would be less than 20 cc)

Sponsors & Collaborators

• Emory University: lead
• Johns Hopkins University: collaborator
• University of Miami: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (3)

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Related Publications (3)

• Trivedi AG, Kim SH, Ramesh KK, Giuffrida AS, Weinberg BD, Mellon EA, Kleinberg LR, Barker PB, Han H, Shu HG, Shim H, Schreibmann E. Applying a Radiation Therapy Volume Analysis Pipeline to Determine the Utility of Spectroscopic MRI-Guided Adaptive Radiation Therapy for Glioblastoma. Tomography. 2023 May 21;9(3):1052-1061. doi: 10.3390/tomography9030086.

  PMID: 37218946 DERIVED

• Ramesh K, Gurbani SS, Mellon EA, Huang V, Goryawala M, Barker PB, Kleinberg L, Shu HG, Shim H, Weinberg BD. The Longitudinal Imaging Tracker (BrICS-LIT):A Cloud Platform for Monitoring Treatment Response in Glioblastoma Patients. Tomography. 2020 Jun;6(2):93-100. doi: 10.18383/j.tom.2020.00001.

  PMID: 32548285 DERIVED

• Gurbani S, Weinberg B, Cooper L, Mellon E, Schreibmann E, Sheriff S, Maudsley A, Goryawala M, Shu HK, Shim H. The Brain Imaging Collaboration Suite (BrICS): A Cloud Platform for Integrating Whole-Brain Spectroscopic MRI into the Radiation Therapy Planning Workflow. Tomography. 2019 Mar;5(1):184-191. doi: 10.18383/j.tom.2018.00028.

  PMID: 30854456 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Radiotherapy; Magnetic Resonance Spectroscopy; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Hui-Kuo Shu
• Organization: Emory University

hgshu@emory.edu

4047781900

Study Officials

• Hui-Kuo Shu, MD, PhD

  Emory University/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: May 3, 2017
• Study Start: September 20, 2017
• Primary Completion: September 9, 2024
• Study Completion: September 9, 2024
• Last Updated: August 3, 2025
• Results First Posted: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)